Spread of imipenem-resistant Acinetobacter baumannii co-expressing OXA-23 and GES-11 carbapenemases in Lebanon

© 2015 The Authors. Objectives: The acquisition of carbapenemases by Acinetobacter baumannii is reported increasingly worldwide, but data from Lebanon are limited. The aims of this study were to evaluate the prevalence of imipenem-resistant A. baumannii in Lebanon, identify resistance determinants, and detect clonal relatedness. Methods: Imipenem-resistant A. baumannii were collected from nine Lebanese hospitals during 2012. Antimicrobial susceptibility, the cloxacillin effect, and ethylenediaminetetraacetic acid (EDTA) synergy were determined. Genes encoding carbapenemases and insertion sequence IS. Aba1 were screened via PCR sequencing. IS. Aba1 position relative to genes encoding Acinetobacter-derived cephalosporinases (ADCs) and OXA-23 was studied by PCR mapping. Clonal linkage was examined by enterobacterial repetitive intergenic consensus PCR (ERIC-PCR). Results: Out of 724 A. baumannii isolated in 2012, 638 (88%) were imipenem-resistant. Of these, 142 were analyzed. Clavulanic acid-imipenem synergy suggested carbapenem-hydrolyzing extended-spectrum β-lactamase. A positive cloxacillin test indicated ADCs, while EDTA detection strips were negative. Genotyping indicated that 90% of isolates co-harbored blaOXA-23 and blaGES-11. The remaining strains had blaOXA-23, blaOXA-24, blaGES-11, or blaOXA-24 with blaGES-11. ISAba1 was located upstream of blaADC and blaOXA-23 in 97% and 100% of isolates, respectively. ERIC-PCR fingerprinting revealed 18 pulsotypes spread via horizontal gene transfer and clonal dissemination. Conclusion: This survey established baseline evidence of OXA-23 and GES-11-producing A. baumannii in Lebanon, indicating the need for further surveillance

Countrywide spread of OXA-48 carbapenemase in Lebanon: Surveillance and genetic characterization of carbapenem-non-susceptible Enterobacteriaceae in 10 hospitals over a one-year period

© 2014 The Authors. Objectives: To detect, characterize, and assess the genetic clonality of carbapenem-non-susceptible Enterobacteriaceae in 10 Lebanese hospitals in 2012. Methods: Selected Enterobacteriaceae isolates with reduced susceptibility to carbapenems were subject to phenotypic study including antibiotic susceptibility, cloxacillin effect, modified Hodge test, and activity of efflux pump inhibitor. Carbapenemase genes were detected using PCR; clonal relatedness was studied by pulsed field gel electrophoresis. Results: Out of 8717 Enterobacteriaceae isolated in 2012, 102 (1.2%) showed reduced susceptibility to carbapenems. Thirty-one (70%) of the 44 studied clinical isolates harbored blaOXA-48, including 15 Klebsiella pneumoniae, eight Escherichia coli, four Serratia marcescens, three Enterobacter cloacae, and one Morganella morganii. The majority of OXA-48 producers co-secreted an extended-spectrum beta-lactamase, while one had an acquired AmpC of the ACC type. In the non-OXA-48 producers, carbapenem resistance was attributed to the production of acquired AmpC cephalosporinases of MOX or CIT type, outer membrane impermeability, and/or efflux pump overproduction. DNA fingerprints revealed that OXA-48 producers were different, except for clonal relatedness among four K. pneumoniae, two E. coli, two E. cloacae, and three S. marcescens. Conclusions: Nosocomial carbapenem-non-susceptible Enterobacteriaceae are moderately spread in Lebanon and the predominant mechanism is OXA-48 production

Continuum-mechanical, Anisotropic Flow model for polar ice masses, based on an anisotropic Flow Enhancement factor

A complete theoretical presentation of the Continuum-mechanical, Anisotropic Flow model, based on an anisotropic Flow Enhancement factor (CAFFE model) is given. The CAFFE model is an application of the theory of mixtures with continuous diversity for the case of large polar ice masses in which induced anisotropy occurs. The anisotropic response of the polycrystalline ice is described by a generalization of Glen's flow law, based on a scalar anisotropic enhancement factor. The enhancement factor depends on the orientation mass density, which is closely related to the orientation distribution function and describes the distribution of grain orientations (fabric). Fabric evolution is governed by the orientation mass balance, which depends on four distinct effects, interpreted as local rigid body rotation, grain rotation, rotation recrystallization (polygonization) and grain boundary migration (migration recrystallization), respectively. It is proven that the flow law of the CAFFE model is truly anisotropic despite the collinearity between the stress deviator and stretching tensors.Comment: 22 pages, 5 figure

Crowdsourced mapping of unexplored target space of kinase inhibitors

Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome. The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts